Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. It can be broadly sub-classified into nonalcoholic fatty liver (NAFL), which is thought to have minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), which is thought to have an increased risk of progression to cirrhosis. The current diagnostic gold standard for differentiating whether a patient with NAFLD has NAFL versus NASH is liver biopsy. However, liver biopsy is an invasive procedure, which is limited by sampling variability, cost, and may be complicated by morbidity and rarely even death.
Accurate, non-invasive, biomarkers for the detection of NASH are currently not available. Substantially non-invasive (e.g., except for a blood draw) diagnosis of NASH is a major unmet medical need.
Previous studies have shown that lipotoxicity plays an important role in the pathogenesis of NASH. Recent data suggest that oxidized low density lipoprotein (oxLDL) as well as other lipid moieties have been implicated as increased in patients with NASH compared to those with NAFL.
Oxidized polyunsaturated fatty acids (PUFAs) and their metabolites are implicated in a wide range of inflammatory diseases and auto-oxidized linoleic and linolenic acids have been reported in NAFLD. With the recent evolution of liquid chromatographic-mass spectrometric based lipidomics techniques, a robust and comprehensive approach to the lipidomics analysis of hundreds of fatty acids, acylethanolamines and inflammatory eicosanoids, including their numerous metabolites arising from an array of cyclooxygenases, lipoxygenases, cytochrome P450s and non-enzymatic oxidations producing isoprostanes, as well as combinations thereof has been developed. Particular attention has been focused on the eicosanoids and related oxygenated metabolites derived from arachidonic acid (AA) and other PUFAs. Over 150 such metabolites can now be routinely quantified.
Patients diagnosed with NASH have an increased risk of developing cirrhosis. There is currently no cure for cirrhosis and patients are limited to treatments which can delay the progress of the disease, minimize damage to liver cells and reduce complications. Early diagnosis of NASH can halt progression of the disease and prevent progression to cirrhosis. However, the only method currently available to reliably diagnose NASH is liver biopsy, a very invasive procedure.